Regeneron Announces Positive Results from its Phase 3 OPTIMA Clinical Trial

By Dr Andrew Rankin, Trustee

On Wednesday 17 September 20205, Regeneron announced very positive results from their Phase 3 pivotal clinical trial in adults 18 and over with FOP.

The trial tested two doses of garetosmab, 3 and 10 mg, versus a placebo via four-weekly intravenous infusions, for 56 weeks.  The activin A monoclonal antibody garetosmab demonstrated up to 99% reduction of abnormal bone formation compared with the placebo.

The trial has shown that garetosmab is the first and only experimental therapy to bring a drastic reduction in both the number and volume of abnormal bone formation (heterotopic ossification) in people living with FOP.

A pivotal trial is required by regulatory agencies such as the US Food and Drug Administration and the UK MHRA in order to approve a drug for marketing approval and for it to be allowed to be used in that country.

You can read the full press release here: https://newsroom.regeneron.com/news-releases/news-release-details/regeneron-announces-positive-phase-3-trial-adults-ultra-rare

In summary, the key points are:

Both doses of garetosmab have proven to be highly effective in reducing the number of new bone lesions by greater than 90% compared to placebo.

It has achieved a reduction of more than 99% of the total volume of new bone injuries.

 The increased dose of 10 mg/kg has also reduced painful flare-ups by 89%.

 The impact is such that the Independent Data Monitoring Committee has recommended that patients who were treated with placebo switch to garetosmab as soon as possible to obtain benefit.

Professor Richard Keen, who we know well from the Royal National Orthopaedic Hospital, stated that “these trial results clearly illustrate the potential of garetosmab to alter the disease, reduce new lesions and notably is the first, and only investigational therapy to demonstrate a dramatic reduction in both the number and volume of abnormal bone lesions.”

So, what was that dramatic reduction?  Well, we’re talking about 90 % or more reduction in bone formation however you measure it – either the number of new bone lesions, or the volume of new bone.  Importantly, a secondary endpoint of flare-ups was also reduced by up to 89% on the higher dose of garetosmab.

Should regulatory agencies (including the UK’s MHRA) approve this treatment, their decision on whether to approve the lower or higher dose will be interesting.   The higher dose is more effective for the reduction of flare-ups and bone formation, but also has an increase in the adverse event of skin and soft tissue infections at 10 mg.

While it seems probable the drug will be approved for adults, we must be cautious. This is because Regeneron has only released summary highlights, and we have not yet seen all the data that regulatory agencies will review.

In previous studies of garetosmab, both minor skin and soft tissue infections, and nosebleeds were known side effects. In this study, the higher dose (10mg) did show an increase in skin and soft tissue infection but no difference in the nosebleeds.  It will be interesting to see which dose gets approved.

The submission of the regulatory application for marketing authorisation of garetosmab for the treatment of FOP to the FDA is scheduled for the end of 2025.  Global applications are scheduled for 2026.  Garetosmab has rapid approval designation in the US and EU so, if approved, this could happen as quickly as 6 months in those jurisdictions.  We hope that the UK regulatory agency MHRA will piggyback on those applications to make it available for adults with FOP in the UK as soon as possible, potentially late 2026 or 2027.

The start of a critical Phase 3 study on garetosmab in adolescents and children with FOP, called OPTIMA 2, is also planned for 2026.  We are hopeful that there will be an opportunity for patients in the UK to take part in this trial.  This is paramount as we all recognise that early intervention in children is critical to avoid the severe progressive impact of FOP from a young age.

The success of garetosmab in this study marks a significant advancement for the potential treatment of FOP, offering hope to people affected by this difficult disease, both patients and families.  While regulatory approval is not assured (remembering the regulatory agencies will see the full data that has not yet been released), we remain hopeful for a positive outcome within the next year.

I’m sure the FOP community would like to thank everyone who contributed to this process, from the researchers, doctors, patients, and families who participated in the study to the persistent and skilled medical scientists at Regeneron and other companies around the globe.

These results are very exciting and give our community great hope.   This is the first truly active potential medicine for treating patients with FOP.

Let’s hope for favourable regulatory reviews, approval for marketing and an early paediatric clinical trial that also recruits in the UK.

Dr Andrew Rankin

FOP Friends Trustee

With thanks also to FOP Italia for part of the summary